Is L-Lactate a Novel Signaling Molecule in the Brain?. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Mosienko, Valentina; Teschemacher, Anja G; Kasparov, Sergey
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 35:Issue 7(2015)
• Page Start: 1069
• Page End: 1075
• Publication Date: 2015-07
• Subjects: astrocytes -- ATP -- brain slice -- lactate -- optogenetics; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2015.77
• Languages: English
• ISSNs: 0271-678X

Abstract

In the brain, L-lactate is produced by both neurons and astrocytes. There is no doubt that neurons use L-lactate as a supplementary fuel although the importance of this energy source is disputed. Irrespective of its caloric value, L-lactate might also have a signaling role in the brain. Here, we review several current hypotheses of L-lactate mediated signaling. Some proposed mechanisms require L-lactate entry into the neurons leading to a shift in ATP/ADP ratio or redox state. Others postulate interaction with either known receptor HCA1 (GPR81) or a novel, yet unidentified receptor. We argue that the sensitivity of any such mechanism has to match the concentration range of extracellular L-lactate, which is less than ~ 1.5 mmol/L under physiologic conditions. From that point of view, some of the proposed mechanisms require supraphysiologic levels of L-lactate and could be engaged during ischemia or seizures when L-lactate concentration rises dramatically. Currently, we do not know whether L-lactate production in the brain occurs in microdomains, which might create higher than average local concentrations. Nevertheless, it is clear that in the brain, as in the peripheral tissues, L-lactate is not only used as a source of energy but also acts as a signaling molecule.